Anti-inflammatory activity of verbascoside- and isoverbascoside-rich Lamiales medicinal plants.

Verbascoside and isoverbascoside are two active phenylethanoid glycosides mainly found in plants of the order Lamiales. This study analyzes the verbascoside and isoverbascoside levels and the total phenolic contents in the water and ethanolic extracts of 20 medicinal plants of the order Lamiales commonly used in Thailand. The related bioactivities, including the antioxidant activity via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction activity potential assays and anti-tyrosinase and -inflammatory activities via the cyclooxygenase and nitric oxide assays are also investigated. The extracts of several plant species, including Barleria prionitis, B. lupulina, Rhinacanthus nasutus, Orthosiphon aristatus, and Nicoteba betonica, exhibit high verbascoside and isoverbascoside content levels. The correlation analysis between the bioactive activities and the active compounds demonstrates a significant association between the verbascoside level in the water extracts and both the DPPH antioxidant activity and the nitric oxide level in the anti-inflammatory assays. This study provides the first report on the verbascoside and isoverbascoside quantification of several plant samples. The findings provide valuable insights for future research on lesser-studied plants possessing high verbascoside and isoverbascoside levels, which exhibit promising anti-inflammatory activities.

Correction: Analysis of canthin-6-one alkaloids derived from Eurycoma spp. by micellar liquid chromatography and conventional high-performance liquid chromatography: a comparative evaluation.

[This corrects the article DOI: 10.1039/D2RA07034K.].

Analysis of canthin-6-one alkaloids derived from Eurycoma spp. by micellar liquid chromatography and conventional high-performance liquid chromatography: a comparative evaluation.

Extracts of Eurycoma longifolia Jack (EL) and Eurycoma harmandiana Pierre (EH) contain numerous bioactive compounds and varying matrices that are challenging to separate using chromatographic techniques. Herein, micellar liquid chromatography (MLC) was used to analyze canthin-6-one alkaloids contained in these extracts, and the achieved performance was compared with that of a conventional high-performance liquid chromatography (HPLC) method. The optimal mobile phase of MLC corresponded to 15 : 85 (v/v) acetonitrile : water (pH 3) containing 110 mM sodium dodecyl sulfate and 10 mM NaH2PO4. The retention times of canthin-6-one-9-O-ß-d-glucopyranoside, 9-hydroxycanthin-6-one, canthin-6-one, and 9-methoxycanthin-6-one were 4.78/15.42, 17.64/24.11, 32.84/38.27, and 39.04/39.86 min, respectively, in the cases of isocratic MLC and conventional HPLC. In both cases, the analyte resolution exceeded 1.5. The MLC elution behavior of the examined analytes was largely determined by their hydrophobicity and ionization. The sensitivity, precision, accuracy, and per-run acetonitrile consumption of the MLC method were comparable to those of the conventional HPLC method. However, the latter method exhibited higher performance for application to EL and EH samples, particularly those with low analyte concentrations and varying sample matrices. Overall, the analysis of canthin-6-one alkaloids using MLC was limited to trace analytes due to interference by the matrix.

Evaluating the in Vitro Efficacy of Quassinoids from Eurycoma longifolia and Eurycoma harmandiana against Common Cold Human Coronavirus OC43 and SARS-CoV-2 Using In-Cell Enzyme-Linked Immunosorbent Assay.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has become a pandemic and public health crisis. SARS-CoV-2 and the seasonal common cold coronavirus (HCoV-OC43) belong to the beta genus of human coronaviruses (HCoVs). In-cell ELISA assays were performed using HCoV-OC43 and SARS-CoV-2 and evaluated the antiviral activity of herbal plants. Eurycoma longifolia (EL) and Eurycoma harmandiana (EH) roots (antipyretic properties) and their constituent quassinoids, especially chaparrinone and eurycomalactone, showed potent anti-HCoV-OC43 and SARS-CoV-2 activities, and the low IC50 values of the mentioned constituents were observed in the range of 0.32-0.51 µM. Eurycomanone and 13ß,21-dihydroeurycomanone may contribute to the antiviral activity of EL, whereas chaparrinone is the major and active antiviral constituent of EH root. The content of quassinoids, ß-carboline, and canthin-6-one alkaloids and the cytotoxicity profile of EL and EH extracts were varied regarding extraction solvents. The boiled water and 50% EtOH extractions of both plants were less toxic than those with 95% EtOH as the extraction solvent. Our research suggests that quassinoids, which come from EL and EH roots and are anti-coronavirus compounds, are potential treatment candidates for COVID-19 and merit further in vivo investigations.

Phosphodiesterase-5 Inhibitory Activity of Canthin-6-One Alkaloids and the Roots of Eurycoma longifolia and Eurycoma harmandiana.

Eurycoma longifolia (EL) and Eurycoma harmandiana (EH) are natural medicinal plants belonging to the Simaroubaceae family, and are well-known for their ability to enhance male sexual performance. The present study investigated the phosphodiesterase-5 (PDE-5) inhibitory activity of intact roots of EL and EH. Additionally, canthin-6-one alkaloids, ß-carboline alkaloids, and quassinoids were also screened for PDE-5 inhibitory activity. We developed in vitro root and callus cultures of EL and EH to determine their PDE-5 inhibitory activity. Our results indicated that canthin-6-one alkaloids, which include canthin-6-one-9-O-ß-D-glucopyranoside, 9-methoxycanthin-6-one, canthin-6-one, and 9-hydroxycanthin-6-one, exhibited PDE-5 enzymatic inhibitory activity, with IC50 values of 2.86±0.23, 3.30±1.03, 4.31±0.52, and 4.66±1.13 µM, respectively. The ethanolic extract of the intact roots of EL and EH, and the in vitro root culture of EH had large amounts of canthin-6-one alkaloids (1.50±0.04, 2.12±0.03, and 3.48±0.08 mg/g dry weight, respectively), and showed potent PDE-5 inhibition. Our findings indicate that in vitro root cultures of EH may be used to replace intact plants, and canthin-6-one-9-O-ß-D-glucopyranoside should be further investigated for development as a health supplement.

HPLC-UV-Based Simultaneous Determination of Canthin-6-One Alkaloids, Quassinoids, and Scopoletin: The Active Ingredients in Eurycoma Longifolia Jack and Eurycoma Harmandiana Pierre, and Their Anti-Inflammatory Activities.

BACKGROUND: Quassinoids and canthin-6-one alkaloids are bioactive markers of Eurycoma longifolia (EL) and E. harmandiana (EH) and have been commercially utilized to treat inflammation and male infertility. OBJECTIVES: This study aims to reveal the contents of bioactive compounds and compare anti-inflammatory activities of these two species. METHODS: HPLC methods coupled with UV-Vis detection were developed and validated for the simultaneous analysis of the chemical profiles and their contents in EL and EH. The anti-inflammatory activities of both species were investigated using RAW 264.7 cell line. RESULTS: The HPLC methods provided a sensitivity (LOD) of 0.02-0.05 µg/mL for the eight bioactive compounds (canthin-6-one alkaloids, quassinoids, and scopoletin) with high precision (% relative standard deviation (RSD) ≤6.48) and recoveries between 80.0 and 120%. The chaparrinone: eurycomanone ratio was high in EH, whereas EL had a higher ratio of eurycomanone: chaparrinone than EH. The contents of total canthin-6-one alkaloids, quassinoids, and scopoletin were 0.01-0.75, 0.19-1.54, and 0.01-0.28 mg/g, respectively, in EL roots and 0.12-1.80, 7.05-9.26, and 0.02 mg/g, respectively, in EH roots. The anti-inflammatory effects of EL and EH extracts varied among the samples due to the variation in their chemical constituents. CONCLUSIONS: In summary, our study indicated that chaparrinone was the major compound in EH. EH exhibited anti-inflammatory activity to the same extent as EL. HIGHLIGHTS: EH and EL extracts were analyzed using developed HPLC-UV methods, revealing a high concentration of chaparrinone in EH, and an anti-inflammatory assay indicated that EH had a potency comparable to that of EL.

Phenylethanoid and flavone glycosides from Ruellia tuberosa L.

A new phenylethanoid glycoside, isocassifolioside (8), and two new flavone glycosides, hispidulin 7-O-α-L-rhamnopyranosyl-(1'″ → 2″)-O-ß-D-glucuronopyranoside (11) and pectolinaringenin 7-O-α-L-rhamnopyranosyl-(1'″ → 2″)-O-ß-D-glucuronopyranoside (12) were isolated from the aerial portions of Ruellia tuberosa L., together with verbascoside (1), isoverbascoside (2), nuomioside (3), isonuomioside (4), forsythoside B (5), paucifloside (6), cassifolioside (7), hispidulin 7-O-ß-D-glucuronopyranoside (9) and comanthoside B (10). The structure elucidations were based on analyses of chemical and spectroscopic data including 1D- and 2D-NMR. The isolated compounds 1-12 exhibited radical scavenging activity using ORAC assay.

Unprecedented furan-2-carbonyl C-glycosides and phenolic diglycosides from Scleropyrum pentandrum.

Five unprecedented furan-2-carbonyl C-glycosides, scleropentasides A-E, and two phenolic diglycosides, 4-hydroxy-3-methoxybenzyl 4-O-ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside and 2,6-dimethoxy-p-hydroquinone 1-O-ß-D-xylopyranosyl-(1→6)-ß-d-glucopyranoside, were isolated from leaves and twigs of Scleropyrum pentandrum together with potalioside B, luteolin 6-C-ß-D-glucopyranoside (isoorientin), apigenin 8-C-ß-D-glucopyranoside (vitexin), apigenin 6,8-di-C-ß-D-glucopyranoside (vicenin-2), apigenin 6-C-α-L-arabinopyranosyl-8-C-ß-D-glucopyranoside (isoschaftoside), apigenin 6-C-ß-D-glucopyranosyl-8-C-ß-D-xylopyranoside, adenosine and l-tryptophan. Structure elucidations of these compounds were based on analyses of chemical and spectroscopic data, including 1D and 2D NMR. In addition, the isolated compounds were evaluated for their radical scavenging activities using both DPPH and ORAC assays.

3-Hydroxydihydrobenzofuran glucosides from Gnaphalium polycaulon.

A new 3-hydroxydihydrobenzofuran glucoside, gnaphaliol 9-O-ß-D-glucopyranoside (2), was isolated from the aerial parts of Gnaphalium polycaulon together with 1-{(2R*,3S*-3-(ß-D-glucopyranosyloxy)-2,3-dihydro-2-[1-(hydroxyl methyl)vinyl]-1-benzofuran-5-yl}-ethanone or gnaphaliol 3-O-ß-D-glucopyranoside (1), (Z)-3-hexenyl O-ß-D-glucopyranoside (3) and adenosine (4). The absolute configurations at C-2 and C-3 positions of compound 1 were determined to be 2R and 3R. The structures of these compounds were elucidated on the basis of their physical and spectroscopic data.

Unusual glycosides of pyrrole alkaloid and 4'-hydroxyphenylethanamide from leaves of Moringa oleifera.

Glycosides of pyrrole alkaloid (pyrrolemarumine 4″-O-α-L-rhamnopyranoside) and 4'-hydroxyphenylethanamide (marumosides A and B) were isolated from leaves of Moringa oleifera along with eight known compounds; niazirin, methyl 4-(α-L-rhamnopyranosyloxy)benzylcarbamate, benzyl ß-D-glucopyranoside, benzyl ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside, kaempferol 3-O-ß-D-glucopyranoside, quercetin 3-O-ß-D-glucopyranoside, adenosine and L-tryptophan. Structure elucidations were based on analyses of chemical and spectroscopic data including 1D- and 2D-NMR.

Acanmontanoside, a new phenylethanoid diglycoside from Acanthus montanus.

A new phenylethanoid glycoside acylated with syringic acid, namely acanmontanoside, was isolated from the aerial portions of Acanthus montanus (Nees). T. Anderson, along with decaffeoylverbascoside, verbascoside, isoverbascoside, leucosceptoside A, (2R)-2-O-ß-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (HBOA-Glc), (2R)-2-O-ß-D-glucopyranosyl-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA-Glc), (3R)-1-octen-3-ol-3-O-ß-D-xylopyranosyl-(1→6)-O-ß-D-glucopyranoside and ebracteatoside B. The structure elucidations were based on physical data and spectroscopic analyses including 1D- and 2D-NMR.

L-(-)-(N-trans-cinnamoyl)-arginine, an acylamino acid from Glinus oppositifolius (L.) Aug. DC.

An amino acid derivative, L-(-)-(N-trans-cinnamoyl)-arginine, was isolated from the whole plant of Glinus oppositifolius (L.) Aug. DC. along with kaempferol 3-O-galactopyranoside, isorhamnetin 3-O-beta-D-xylopyranosyl-(1-->2)-beta-D-galactopyranoside, vitexin, vicenin-2, adenosine and L-phenylalanine. The structure determinations were based on analyses of chemical and spectroscopic methods.

Antioxidant, antibacterial and antigiardial activities of Walsura robusta Roxb.

Walsura robusta Roxb. (Family: Meliaceae) is a well-known multi-purpose medicinal plant, and has been employed for a wide range of disease conditions without documented scientific data. In the current study, four pure isolated compounds, 3,4,5-trimethoxyphenyl beta-D-glucopyranoside (1), turpinionoside A (2), (+)-lyoniresinol 3alpha-O-beta-D-glucopyranoside (3) and (-)-lyoniresinol 3alpha-O-beta-D-glucopyranoside (4), were isolated from the leaves and twigs of W. robusta. Biological evaluation for free radical scavenging, antibacterial and antigiardial activities was performed. We investigated antioxidant effects of the crude extracts as well as the isolated compounds using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), hydroxyl radical (OH), and superoxide anion (O(2)) scavenging assays. Three phenolic glucosides (1, 3 and 4) were found to possess strong antioxidant activity. They scavenged DPPH(*) with IC(50) values in the range of 51.5-86.6 microM. We also detected the superoxide dismutase-like activities in compounds 3 and 4 which are lignan glucosides, demonstrating potent superoxide scavenging activity with IC(50) values in the range of 0.8 and 0.7 microM, respectively. Other biological activities including antibacterial and antigiardial assays were carried out. Preliminary results demonstrated that most extracts, except the diethyl ether extract, exhibited inhibition zones against all Gram-positive bacteria including Bacillus cereus, Staphylococcus aureus, Streptococcus mutans, and S. pyogenes. Aqueous extracts of this plant species could inhibit Gram-positive and some Gram-negative bacteria such as Escherichia coli, Salmonella typhi and Shigella sonnei. However, the determination of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of W. robusta on all tested bacterial strains showed only weak activity, and their MBCs were greater than 25 mg mL(-1). For antigiardial activity, incubation with 2 x 10(5) trophozoites mL(-1) of the culture medium with the crude extracts at concentration ranged from 31.25 to 1000 microg mL(-1) demonstrated no activity (MIC > 1000 microg mL(-1)).

Evaluation of chikusetsusaponin IVa isolated from Alternanthera philoxeroides for its potency against viral replication.

Chikusetsusaponin IVa and calenduloside E were isolated from the whole plant of Alternanthera philoxeroides (Mart.) Griseb (Amaranthaceae) and evaluated for their antiviral activities. Chikusetsusaponin IVa showed antiviral activities against HSV-1, HSV-2, human cytomegalovirus, measles virus, and mumps virus with selectivity indices (CC (50)/IC (50)) of 29, 30, 73, 25, and 25, respectively. On the other hand, calenduloside E showed no antiviral effects against any of the viruses tested. The mode of HSV-2 action of chikusetsusaponin IVa was determined under different experimental conditions. The anti-HSV-2 target of the compound might be mainly related to direct inactivation of virus particles and to the inhibition of release of progeny viruses from infected cells, but it is not related to inhibition of viral attachment, cell penetration, and viral protein synthesis. This compound also provided in vivo efficacy in a mouse model of genital herpes caused by HSV-2. These results demonstrate that chikusetsusaponin IVa might be a candidate of antiherpetic agents.

Chemical constituents from Oldenlandia corymbosa L. of Thai origin.

From the whole plants of Oldenlandia corymbosa of Thai origin, ten compounds have been isolated and elucidated as geniposide, 6 alpha-hydroxygeniposide, scandoside methyl ester (6 beta-hydroxygeniposide), asperulosidic acid, deacetylasperuloside, asperuloside, 10-O-benzoylscandoside methyl ester, 10-O-p-hydroxybenzoylscandoside methyl ester, (+)-lyoniresinol-3 alpha-O-beta-glucopyranoside, and rutin. Their structures were determined on the basis of spectroscopic data.

Megastigmane and flavone glycosides from Strophioblachia fimbricalyx Boerl.

Three megastigmane glucosides, bridelionoside B, ampelopsisionoside and 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside, together with three flavone glycosides, apigenin 7-O-beta-D-glucopyranoside, isovitexin and spinosin, were isolated from the aerial portions of Strophioblachia fimbricalyx. The structure determinations were based on physical data and spectroscopic evidence.

Tricalysiosides P-U: Ent-kaurane glucosides and a labdane glucoside from leaves of Tricalysia dubia OHWI.

Further extensive isolation work on the 1-BuOH-soluble fraction of a MeOH extract of Tricalysia dubia afforded five new ent-kaurane glucosides (4-8) and one new labdane glucoside (9), together with a known megastigmane glucoside, sammangaoside B (1), and monoterpene glucosides (2, 3). The structures of the new compounds were elucidated by analyses of one- and two-dimensional NMR spectroscopic data. The absolute configuration of the 9-position of sammangaoside B was revised to S and its total stereochemistry was established by the modified Mosher's method.

Megastigmane glucosides from Equisetum debile and E. diffusum.

A new megastigmane diglucoside, (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3,9-O-beta-D-diglucopyranoside (3), was isolated from the aerial portion of Equisetum debile along with macarangioside D (debiloside A), sammangaoside A, (6R,9S)-3-oxo-alpha-ionol 9-O-beta-D-glucopyranoside, debiloside B, kaempferol 3-O-sophoroside, kaempferol 3,7-O-beta-D-diglucopyranoside, kaempferol 3-O-sophoroside-7-O-beta-D-glucopyranoside, phenylethyl O-beta-D-glucopyranoside, (Z)-3-hexenyl O-beta-D-glucopyranoside, (7S,8R)-dehydrodiconiferyl 4-O-beta-D-glucopyranoside, and L-tryptophan. The absolute configuration at C-6 of the original structure of debilo-side A was revised to 6R-configuration, and was identical with macarangioside D (1). From the aerial portion of E. diffusum, four compounds, sammangaoside A, kaempferol 3-O-sophoroside and L-tryptophan and (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside were identified. The spectroscopic data of (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside (13) were found to be identical with corchoionoside A (9R-isomeric compound). The structure of corchoionoside A was also discussed. Structure determinations were based on physical data and spectroscopic evidence.

Aromatic diglycosides from Cladogynos orientalis.

Two unusual aromatic diglycosides with galloyl substitution, 4''-O-galloyl-violutoside and 4''-O-galloyl-benzyl-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside, were isolated from the aerial portion of Cladogynos orientalis along with isovitexin, apigenin 6-C-(2''-O-galloyl)-beta-D-glucopyranoside, apigenin 8-C-(2''-O-galloyl)-beta-D-glucopyranoside, syringic acid beta-D-glucopyranoside, 3,4,5-trimethoxyphenyl beta-D-glucopyranoside, (6S,9R)-roseoside, and violutioside. The structural elucidations were based on analyses of chemical and spectroscopic data by including 1D and 2D NMR analyses.

Lignan, phenolic and iridoid glycosides from Stereospermum cylindricum.

A lignan glycoside [(+)-cycloolivil 4'-O-beta-d-glucopyranoside], a phenolic glycoside [3,4-dimethoxyphenyl 1-O-beta-d-xylopyranosyl-(1-->6)-beta-d-glucopyranoside] and a iridoid glycoside (stereospermoside) were isolated from the leaves and branches of Stereospermum cylindricum, together with (+)-cycloolivil, (+)-cycloolivil 6-O-beta-d-glucopyranoside, (-)-olivil, (-)-olivil 4-O-beta-d-glucopyranoside, (-)-olivil 4'-O-beta-d-glucopyranoside, vanilloloside, decaffeoyl-verbascoside, isoverbascoside, 3,4,5-trimethoxyphenyl 1-O-beta-d-xylopyranosyl-(1-->6)-beta-d-glucopyranoside, ajugol, verminoside, and specioside. The structure elucidations were based on spectroscopic evidence.